Inhibition of multiplication of Toxoplasma gondii by human monocytes exposed to T-lymphocyte … (original) (raw)
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Survival of immunoglobulin G-opsonized Toxoplasma gondii in nonadherent human monocytes
Infection and Immunity, 1995
Toxoplasma gondii is a protozoan parasite that is able to penetrate human monocytes by either passive uptake during phagocytosis or active penetration. It is expected that immunoglobulin G (IgG) opsonization will target the parasite to macrophage Fc gamma receptors for phagocytic processing and subsequent degradation. Antibody-opsonized T. gondii tachyzoites were used to infect nonadherent and adherent human monocytes obtained from the peripheral blood of seronegative individuals. The infected monocytes were evaluated for the presence of intracellular parasites and the degree of parasiticidal activity. A marked difference in both the numbers of infected macrophages and numbers of parasites per 100 macrophages was observed in the nonadherent cells when compared with those of the adherent cell population. When macrophage Fc gamma receptors were down-modulated, opsonized tachyzoites retained their ability to penetrate the host cell at a rate similar to that observed for unopsonized par...
The Journal of Immunology
C57BL/6 mice chronically infected with an avirulent strain (ME-49) of Toxoplasma gondii were used to study the mechanisms by which T lymphocytes and IFN-gamma prevent reactivation of latent infection. Infected animals were treated with mAb, either anti-CD8, anti-CD4, anti-CD4 plus anti-CD8, anti-IFN-gamma, or anti-CD4 plus anti-IFN-gamma and the mice followed for survival, histopathology, cyst numbers, and spleen cell cytokine responses. In agreement with previously published findings, treatment with anti-IFN-gamma antibodies fully reactivated the asymptomatic infection, inducing massive necrotic areas in the brain with the appearance of free tachyzoites and death of all animals within 2 wk. Mice treated with the combination of anti-CD4 plus anti-CD8 antibodies showed augmented pathology and mortality nearly identical to the anti-IFN-gamma- treated animals. In contrast, treatment with anti-CD4 or anti-CD8 mAb alone failed to result in significantly enhanced brain pathology or mortal...
Demonstration of T-Cell dysfunction during acute toxoplasma infection
Cellular Immunology, 1986
Mice were infected with the virulent RH and the relatively avirulent C56 strains of Toxoplasma gondii (TG). The concanavalin A (Con A)-stimulated lymphoproliferative response of these animals and interleukin-2 (IL2) production by their lymphocytes were assessed 3 and 6 days postinfection. The proliferative response of splenocytes (SC) and T-enriched cells from all infected groups was significantly (P < 0.05-0.005) depressed. Partial removal of macrophages (m$) or addition of indomethacin had no effect on the depressed proliferative response of SC from mice infected with the RH strain of TG for 6 days (RH6), and only partially improved that from the other infected groups. IL2 production of T-enriched cells, obtained by scrupulously removing rn4 using sequential adherence of SC to plastic and nylon wool, was markedly decreased in all infected mice. These data indicate that both rn& and T cells are involved in the immunodepression in toxoplasmosis. Except for the RH6 group, the depressed lymphoproliferative responses of all infected groups were entirely reconstituted by exogenous IL-2, but their peak response never reached that of the control group. Therefore, the decreased lymphoproliferation could not be explained solely by a defect in IL2 production. The proliferative response of the RH6 lymphocytes, in the presence of Con A, was significantly lower than that without Con A at each IL-2 concentration added. This suggests the presence of an active suppressor factor inducible by Con A. The RH strain of TG caused a greater degree of immunodepression than the C56 strain, suggesting an association between the virulence of different strains of TG with their ability to immunosuppress. Q 1986 Academic Press, Inc.
Heterogeneity in cellular and humoral immune responses againstToxoplasma gondiiantigen in humans
Clinical and Experimental Immunology, 2004
SUMMARYProtection against Toxoplasma gondii in infected patients is mainly attributed to cellular immunity. We here attempt to improve the characterization of the proteins that induce cellular immunity in naturally infected patients. Cellular immunity was evaluated by flow cytometry after 7 days of blood culture from 31 chronically T. gondii infected and 8 noninfected pregnant women, in the presence of soluble T. gondii antigen (ST-Ag) or fractionated proteins from ST-Ag, separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Blood cultures from infected patients with ST-Ag induced 39·5 ± 12·7% of activated (CD25+) CD4+ T cells using flow cytometry. This contrasts with the absence of activated CD4+ T cells after either culture with PBS or in blood cultures from noninfected women. The protein fraction between 21 and 41·9 kD induced the highest response (14·7 ± 10·0%). Blood samples from 20 infected and 5 uninfected women were cultured in presence of 12 protein subfr...
Frontiers in Cellular and Infection Microbiology
Toxoplasma gondii ROP16 and ROP18 proteins have been identified as important virulence factors for this parasite. Here, we describe the effect of ROP16 and ROP18 proteins on peripheral blood mononuclear cells (PBMCs) from individuals with different clinical status of infection. We evaluated IFN-γ, IL-10, and IL-1β levels in supernatants from PBMCs cultures infected with tachyzoites of the T. gondii wild-type RH strain or with knockout mutants of the rop16 and rop18 encoding genes (RH rop16 and RH rop18). Cytokine secretion was compared between PBMCs obtained from seronegative individuals (n = 10), with those with chronic asymptomatic (n = 8), or ocular infection (n = 12). We also evaluated if polymorphisms in the genes encoding for IFN-γ , IL-10, IL-1β, Toll-like receptor 9 (TLR9), and purinoreceptor P2RX7 influenced the production of the encoded proteins after ex vivo stimulation. In individuals with chronic asymptomatic infection, only a moderate effect on IL-10 levels was observed when PBMCs were infected with RH rop16, whereas a significant difference in the levels of inflammatory cytokines IFN-γ and IL-1β was observed in seronegative individuals, but this was also dependent on the host's cytokine gene polymorphisms. Infection with ROP16-deficient parasites had a significant effect on IFN-γ production in previously non-infected individuals, suggesting that ROP16 which is considered as a virulence factor plays a role during the primary infection in humans, but not in the secondary immune response.
Specific mediation of cellular immunity to Toxoplasma gondii in somatic cells of mice
Infection and immunity, 1984
Lymphocytes from mice immunized against Toxoplasma gondii protected T. gondii-infected macrophage and kidney cell cultures. After contact with antigens, supernatants of such immune lymphocytes, also contained a factor protective for T. gondii-infected macrophages and kidney cells. Supernatants were protective only when the lymphocytes and kidneys cells were isogeneic. Protection was specific in that supernatants from only T. gondii-immune, but not Besnoitia jellisoni-immune, lymphocytes provided protection against toxoplasmosis. Sixteen to 24 h were required for an appreciable amount of protective factor to be secreted; a similar absorption time was necessary for kidney cells to be protected. Peritoneal lymphocyte lysates, prepared as transfer factor, contained protective substances with a potency similar to that of lymphocyte supernatants, which were also strain restricted in their effect.
Acute and Chronic Phases of Toxoplasma gondii Infection in Mice Modulate the Host Immune Responses
1998
Murine antibody responses to soluble proteins are generally restricted to the immunoglobulin G1 (IgG1) isotype. When mice were infected with Toxoplasma gondii Beverley and concomitantly immunized with a soluble unrelated protein antigen, a modification in the isotypic distribution of antibodies directed against this nonparasite antigen was observed, with a preferential production of IgG2a. Interestingly, when mice were immunized with a soluble protein antigen during the chronic phase (day 40) of infection with T. gondii Beverley, a similar modification in the isotypic distribution of antiprotein antibodies was observed.
Toxoplasmosis, 1993
Cell-mediated immunity has long been recognized to play a crucial role in resistance to Toxoplasma gondii. Nevertheless, it is only within recent years that the events involved in cellular control of acute and chronic infection have begun to be defined. An important breakthrough occurred when Suzuki and Remington [Suzuki et al 1988] discovered the central role played by IFN-y in resistance to new infection as well as in the control of re-activation. While the key effector function of this cytokine has now been confirmed, its mechanism of action remains poorly understood. When spleen cells from infected mice or mice vaccinated with the ts-4 mutant are stimulated in vitro with toxoplasma antigens or mitogen, most of the IFNy produced is derived from CD4+ T lymphocytes [Gazzinelli et al 1991, 1992]. Nevertheless, depletion studies performed in both animal models reveal that removal of CD4 + cells fails to ablate resistance. Simultaneous depletion of CD8 + cells, which produce much smaller quantities of the cytokine in vitro, is necessary for full ablation. Moreover, in the vaccine model, a highly significant loss of resistance occurs in mice depleted of CD8+ cells alone. However, when mice are treated with anti-CD4+ antibodies during as opposed to after vaccination, they fail to display immunity to challenge [Gazzinelli, et al 1991]. These findings are consistent with the hypothesis (Figure 1) that CD4 + cells are not the major effector cells of resistance to T. gondii in vivo, but instead their major role is to provide helper function (presumably in the form of IL-2) to CD8 + effector cells or to act as a secondary source of IFN-y. The reason why CD4+ lymphocytes, which produce high levels ofIFN-y in vitro, are not sufficient to mediate protection in vivo is not clear, but may relate to the